Dupilumab

Dupilumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetIL4 receptor alpha
Names
Trade namesDupixent
Clinical data
Main usesEczema, asthma, nasal polyps[1]
Side effectsPain at site of injection, dry eyes, throat pain, trouble sleeping, red eyes[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B1
  • US: N (Not classified yet)
    Routes of
    use    		Subcutaneous
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa617021
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • US: ℞-only
    • EU: Rx only
    Chemical and physical data
    FormulaC6512H10066N1730O2052S46
    Molar mass146898.98 g·mol−1

    Dupilumab, sold under the brand name Dupixent, is a medication used for eczema (atopic dermatitis), asthma, or nasal polyps.[1] It is used in eczema when topical corticosteroids have not been sufficient.[2] It is given by injection under the skin.[3]

    Common side effects include pain at the site of injection, dry eyes, throat pain, trouble sleeping, and red eyes.[1] Other side effects may include allergic reactions, cold sores, and inflammation of the cornea.[1] Safety in pregnancy is unclear.[4] It is a monoclonal antibody that blocks the target receptors of interleukin 4 (IL4) and interleukin 13 (IL13).[5]

    Dupilumab was approved for medical use in the United States and Europe in 2017.[1][5] In the United Kingdom it costs the NHS about £1,300 every 4 weeks as of 2021.[3] In the United States this amount costs about 3,400 USD.[6]

    Medical uses

    Dupilumab appears to be useful for moderate-to-severe atopic dermatitis for which it is approved in the United States.[7][8] It is also being evaluated for treatment of persistent asthma in adults and adolescents.[8][9] Europe approved it in chronic rhinosinusitis with nasal polyposis (CRSwNP).[10] It may also be used to treat eosinophilic esophagitis.[11]

    Dosage

    It is often used at a dose of 200 to 300 mg every two weeks in adults.[1][3] The initial dose may be doubled.[3]

    Side effects

    Dupilumab can cause several side effects including allergic reactions, conjunctivitis, and keratitis.[12]

    There is one reported case of dupilumab triggering hair growth in a patient with complete hair loss.[13] This is being investigated as an unintended, but positive, side effect.

    One other case reports a possibility of chronic eosinophilic pneumonia associated with dupilumab.[14]

    Some concern of potential worsened COVID-19 disease with patients taking dupilumab have been expressed, but according to one study all patients had mild course of disease.[15]

    Pharmacology

    Mechanism of action

    Dupilumab binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a receptor antagonist.[16] Through blockade of IL-4Rα, dupilumab modulates signaling of both the interleukin 4 and interleukin 13 pathways. In clinical trials, specimens from people receiving dupilumab showed decreased levels of Th2 bio-markers.[17]

    Pharmacokinetics

    Dupilumab shows a non-linear rate in regard to the target.[17] Dupilumab is also reported to have a bioavailability of 64%, with the average concentration occurring one week after injection.[17]

    History

    Development of dupilumab was a joint effort by Regeneron Pharmaceuticals and Sanofi Genzyme,[18] the latter of which provided 130 million dollars to Regeneron for research and development towards monoclonal antibodies.[19]

    The United States Food and Drug Administration granted it priority review status.[20][21] On March 28, 2017, the U.S. Food and Drug Administration approved dupilumab injection to treat adults with moderate-to-severe eczema.[12]

    In October 2016, Regeneron completed a phase III trial comparing dupilumab with topical corticosteroids, in which subjects had a larger decrease in symptoms with both duplimab and topical steroids than with steroids alone.[22]

    Phase III studies were also performed to evaluate the efficacy of dupilumab in combination with topical corticosteroids. In these trials 38% and 36% of patients respectively, met the primary efficacy goal of the trial, compared to 8% and 10% under placebo.[17]

    Phase II trials for asthma treatment showed increased lung function for patients, showing increased forced expiratory volume.[17]

    The FDA considers it to be a first-in-class medication.[23]

    References

    1. 1 2 3 4 5 6 7 "Dupixent- dupilumab injection, solution". DailyMed. 25 June 2020. Archived from the original on 24 March 2021. Retrieved 17 September 2020.
    2. ↑ "Dupilumab Monograph for Professionals". Drugs.com. Retrieved 27 December 2021.
    3. 1 2 3 4 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1301. ISBN 978-0857114105.
    4. ↑ "Dupilumab (Dupixent) Use During Pregnancy". Drugs.com. Archived from the original on 12 August 2021. Retrieved 27 December 2021.
    5. 1 2 "Dupixent". Archived from the original on 28 December 2021. Retrieved 27 December 2021.
    6. ↑ "Dupixent Prices, Coupons and Patient Assistance Programs". Archived from the original on 1 October 2020. Retrieved 27 December 2021.
    7. ↑ Kraft M, Worm M (April 2017). "Dupilumab in the treatment of moderate-to-severe atopic dermatitis". Expert Review of Clinical Immunology. 13 (4): 301–310. doi:10.1080/1744666X.2017.1292134. PMID 28165826. S2CID 3404484.
    8. 1 2 Humbert M, Busse W, Hanania NA (January 2018). "Controversies and opportunities in severe asthma". Current Opinion in Pulmonary Medicine. 24 (1): 83–93. doi:10.1097/MCP.0000000000000438. PMID 29059087. S2CID 4433743.
    9. ↑ Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF, et al. (June 2018). "Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma". The New England Journal of Medicine. 378 (26): 2486–2496. doi:10.1056/nejmoa1804092. PMID 29782217. S2CID 205103217. Archived from the original on 2020-10-27. Retrieved 2021-07-02.
    10. ↑ "Regeneron reports third quarter 2019". Regeneron Pharmaceuticals, Inc. November 5, 2019. Archived from the original on April 26, 2021. Retrieved July 2, 2021.
    11. ↑ Inc, Regeneron Pharmaceuticals. "FDA Grants Dupixent® (dupilumab) Breakthrough Therapy Designation for Eosinophilic Esophagitis". www.prnewswire.com. Archived from the original on 2020-09-29. Retrieved 2020-12-01.
    12. 1 2 "FDA approves new eczema drug Dupixent". FDA. 2019-09-10. Archived from the original on 2017-03-28. Retrieved 2021-07-02.
    13. ↑ Penzi LR, Yasuda M, Manatis-Lornell A, Hagigeorges D, Senna MM (November 2018). "Hair Regrowth in a Patient With Long-standing Alopecia Totalis and Atopic Dermatitis Treated With Dupilumab". JAMA Dermatology. 154 (11): 1358–1360. doi:10.1001/jamadermatol.2018.2976. PMID 30304403.
    14. ↑ Menzella, Francesco; Montanari, Gloria; Patricelli, Giulia; Cavazza, Alberto; Galeone, Carla; Ruggiero, Patrizia; Bagnasco, Diego; Facciolongo, Nicola (2019-07-10). "A case of chronic eosinophilic pneumonia in a patient treated with dupilumab". Therapeutics and Clinical Risk Management. 15: 869–875. doi:10.2147/TCRM.S207402. ISSN 1176-6336. PMC 6636310. PMID 31371974.
    15. ↑ Thangaraju, Pugazhenthan; Venkatesan, Nanditha; Sudha, T. Y. Sree; Venkatesan, Sajitha; Thangaraju, Eswaran (2020-09-10). "Role of Dupilumab in Approved Indications of COVID-19 Patient: an Efficacy-Based Nonsystematic Critical Analysis". Sn Comprehensive Clinical Medicine. 2 (11): 2126–2130. doi:10.1007/s42399-020-00510-x. ISSN 2523-8973. PMC 7483051. PMID 32935079.
    16. ↑ Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. (June 2013). "Dupilumab in persistent asthma with elevated eosinophil levels". The New England Journal of Medicine. 368 (26): 2455–66. doi:10.1056/NEJMoa1304048. PMID 23688323.
    17. 1 2 3 4 5 Shirley M (July 2017). "Dupilumab: First Global Approval". Drugs. 77 (10): 1115–1121. doi:10.1007/s40265-017-0768-3. PMID 28547386. S2CID 207489287.
    18. ↑ "Archive copy". Archived from the original on 2021-05-18. Retrieved 2021-07-02.{{cite web}}: CS1 maint: archived copy as title (link)
    19. ↑ "SEC 10-Q Filing of Regeneron". SEC.gov. 2017-06-30. Archived from the original on 2017-10-21. Retrieved 2017-10-20.
    20. ↑ "Novel Biologic Dupilumab Improves Eczema Symptoms". October 2016. Archived from the original on 11 March 2017. Retrieved 30 October 2017.
    21. ↑ Walker J (2016-05-30). "New Eczema Treatments Could Be Available Soon". Wall Street Journal. ISSN 0099-9660. Archived from the original on 2018-01-05. Retrieved 2016-05-31.
    22. ↑ Hamilton JD, Ungar B, Guttman-Yassky E (2015). "Drug evaluation review: dupilumab in atopic dermatitis". Immunotherapy. 7 (10): 1043–58. doi:10.2217/imt.15.69. PMID 26598956.
    23. ↑ New Drug Therapy Approvals 2017 (PDF) (Report). U.S. Food and Drug Administration (FDA). January 2018. Archived from the original on 23 October 2020. Retrieved 16 September 2020.
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